A CORTICO-AMYGDALA CIRCUIT CONTROLS THE STRIATAL MEMORY SYSTEM SUPPORTING THE EFFECT OF PREDICTIVE LEARNING ON CHOICE BETWEEN ACTIONS

Predictive learning enables environmental stimuli to guide choice between actions in an outcome-specific manner. This process involves a durable form of cellular memory characterized by the accumulation of delta-opioid receptors (DOPR) on cholinergic interneurons (CINs) in the nucleus accumbens shell (NAc-S). While this accumulation isn't required for predictive learning itself, it is later necessary for promoting the influence of that learning on choices between actions. Here, we aimed to delineate the upstream brain regions that control the formation and expression of the DOPR-based memory using the outcome-specific Pavlovian-instrumental transfer (PIT) task. Findings indicated that outcome-specific predictive learning forms the DOPR-based memory through direct projections from the basolateral amygdala (BLA) to the NAc-S. However, silencing this pathway at the time of choice had no effect on outcome-specific PIT, suggesting the BLA doesn't directly control the expression of this memory. The possibility remains that the BLA indirectly exerts control by recruiting an intermediary brain region. Experiments examined the role of the infralimbic cortex (IL), which receives inputs from the BLA and sends dense projections to the NAc-S. Optical silencing of the BLA-to-IL or IL-to-NAc-S pathways at the time of choice abolished outcome-specific PIT. Critically, the same result occurred when one pathway was silenced in one brain hemisphere and the other in the contralateral hemisphere. Overall, we describe a cortico-amygdala circuit that orchestrates both the formation and expression of a striatal memory system that mediates the outcome-specific influence of predictive learning on choices between actions.